Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.

Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to provide an update on the use of diagnostic tests for this condition in clinical practice.

Participants: This subgroup was constituted by the Steering Committee to address key questions related to the diagnosis of PHPT.

Acute and chronic regulation of circulating PTH: significance in health and in disease.

Circulating human parathyroid hormone (PTH) is immunoheterogenous. It is composed of 80% carboxyl-terminal (C) fragments and of 20% PTH(1-84). This composition contrasts with the biological activity of the hormone, which is only related to PTH(1-84), creating a paradox between circulating PTH composition and PTH bioactivity.

Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research.

Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease.

Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms.

Rats(r) with secondary hyperparathyroidism were studied to define the relationship between vitamin D metabolites and rPTH levels measured by 3 different rat ELISAs. Controls and renal failure (RF) rats were on a normal diet, while 2 groups on a low-calcium (-Ca) or a vitamin D-deficient (-D) diet. RF was induced surgically.

Nontruncated amino-terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation.

Objective: Some patients with parathyroid carcinoma present with an over-production of nontruncated amino-terminal (NT-N) parathyroid hormone (PTH), a post-transcriptionally modified form of PTH(1-84). This is usually picked up on an elevated whole (W) PTH (third-generation)/total (T) (second-generation) PTH assay ratio (N > 0·8).

Patients And Design: Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described.

Rat parathyroid hormone (rPTH) ELISAs specific for regions (2-7), (22-34) and (40-60) of the rat PTH structure: influence of sex and age.

Rat (r) PTH ELISAs were used to study the influence of age and sex on rPTH levels and circulating PTH molecular forms separated by HPLC. Standard curves and saturation analysis were undertaken to define epitopes. Rats were sacrificed at approximately 27, 47 and 75days.

Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia.

Objective: To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia.

Background: Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder.

Overproduction and secretion of a novel amino-terminal form of parathyroid hormone from a severe type of parathyroid hyperplasia in uremia.

Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure.

An N-terminal molecular form of parathyroid hormone (PTH) distinct from hPTH(1 84) is overproduced in parathyroid carcinoma.

Background: A new parathyroid hormone (PTH) species, the N-terminal PTH form (N-PTH), is distinct from intact human PTH of 84 amino acid residues [hPTH(1-84)] and is recognized in a 3rd-generation assay of "whole" PTH (wPTH; the 1-2 epitope) but not in a 2nd-generation assay of "total" PTH (tPTH; the 12-18 epitope). N-PTH usually represents <15% of wPTH but can be overproduced in severe primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism. We investigated whether N-PTH is also overproduced in parathyroid cancer and whether N-PTH concentration is influenced by calcimimetic therapy.

Persistent hypercalcemia after parathyroidectomy in an adolescent and effect of treatment with cinacalcet HCl.

Background: Hyperparathyroidism is uncommon in adolescence and is more likely to persist after parathyroidectomy than in adults. Cinacalcet HCl is a new calcimimetic that has been used successfully for the treatment of primary and secondary hyperparathyroidism in adults, but its use in adolescents has not been reported.

Case: A 16 year-old male presented with hypercalcemia that had persisted for 1.

Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

Context: The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical.

Objective: The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH.

Design: CaCl2 and Na citrate were infused in eight volunteers.

Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism.

Background: Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on the PTH/PTHrP type I receptor through a C-PTH receptor. We wanted to determine the N structure of non-(1-84) PTH fragments.

Overproduction of an amino-terminal form of PTH distinct from human PTH(1-84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery.

Objective: Rare patients with severe primary hyperparathyroidism present with large parathyroid tumours, severe hypercalcaemia, very high PTH levels and osteitis fibrosa cystica. Some of these patients display a large amount of C-PTH fragments in circulation and present with a higher C-PTH/I-PTH ratio than seen in less severe cases of primary hyperparathyroidism. We wanted to determine how PTH levels and circulating PTH high-performance liquid chromatography (HPLC) profiles analysed with PTH assays having different epitopes could be affected by medical and surgical treatment in such patients.

Carboxyl-terminal parathyroid hormone fragments: role in parathyroid hormone physiopathology.

Purpose Of Review: Carboxyl-terminal parathyroid hormone (C-PTH) fragments constitute 80% of circulating PTH. Since the first 34 amino acids of the PTH structure are sufficient to explain PTH classical biological effects on the type I PTH/PTHrP receptor and since C-PTH fragments do not bind to this receptor, they have long been considered inactive. Recent data suggest the existence of a C-PTH receptor through which C-PTH fragments exert biological effects opposite to those of human PTH(1-84) on the type I PTH/PTHrP receptor.

Evolution of the parathyroid hormone (PTH) assay--importance of circulating PTH immunoheterogeneity and of its regulation.

Most of what we know on PTH bioactivity has been associated with the first 34 amino acids of the PTH structure acting on the type I PTH/PTHrP receptor, leaving little place to the carboxyl-terminal structure. This reality has dictated the evolution of the PTH assay. The first generation of PTH assays has permitted the description of circulating PTH immunoreactivity and of its acute regulation by calcium concentration.

Evidence that the amino-terminal composition of non-(1-84) parathyroid hormone fragments starts before position 19.

Background: Non-(1-84) parathyroid hormone (PTH) fragments are large C-terminal fragments of PTH with a partially preserved N-terminal structure. They differ from other C-terminal PTH fragments, which do not have an N-terminal structure and do not react in intact PTH assays. We aimed to identify the minimal N-terminal structure common to all non-(1-84) PTH fragments.

Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to hPTH(1-84) is overproduced in primary and secondary hyperparathyroidism.

Background: To separate non-(1-84)parathyroid hormone [non-(1-84)PTH] from PTH(1-84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1-84) could be separated into two entities recognized by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure.

Methods: Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15-20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65-84) structure requirement were used to measure basal and fractionated PTH values.

Parathyroid hormone metabolites in renal failure: bioactivity and clinical implications.

Non-(1-84) parathyroid hormones (PTHs) are large circulating carboxyl-terminal PTH (C-PTH) fragments with a partially preserved amino-terminal structure. They were discovered during high-performance liquid chromatography (HPLC) analysis of circulating PTH molecular forms detected by an intact PTH (I-PTH) assay. Like other C-PTH fragments, they accumulate in blood in renal failure and account for up to 50% of I-PTH.